Several polypeptide growth factors have been identified with the ability to induce blood vessel development (angiogenesis), and the overall project goal is to utilize such growth factors to facilitate coronary collateral development in patients with ischemic heart disease. We have shown that basic fibroblast growth factor (bFGF), a pluripotent mitogen of mesodermally-derived cells, and vascular endothelial growth factor (VEGF), a specific endothelial cell mitogen, enhance coronary coronary collateral development in dogs. Based on these investigations, we began a Phase I clinical trial of bFGF in July 1995. We evaluated bFGF pharmacokinetics, pharmacodynamics, tolerability and safety in 25 pts randomized to a single dose of bFGF or placebo (in a 2:1 ratio), infused into a coronary artery over 1 minute. Consecutive cohorts received 3, 10, 30 and 100 mcg/kg bFGF. Plasma clearance was 20 +/- mL/min/kg (mean +/- SD); serum elimination t 1/2 was 85 +/- 29 minutes. bFGF caused an acute 5-18% decrease in MAP that was well-tolerated and independent of dose. bFGF induced an increase in epicardial coronary diameter (2.0 +/- 0.5 to 2.2 +/- 0.5 mm, P<.02). In the 30 mcg/kg cohort, 3 pts had bradycardia 15-96 hours after bFGF; in 2 of 3 there were transient conduction abnormalities and associated symptoms. Two pts had atrial fibrillation approximately 36 hours after bFGF. One pt had an unexplained 15-20% decrease in blood pressure, 45-56 hours after bFGF administration. Mild, transient thrombocytopenia was observed at bFGF doses </= 30 mcg/kg. One pt who received 100 mcg/kg bFGF developed extreme fatigue, orthostasis (-15 mm Hg), nausea and headache. No pts exhibited retinal neovascularization, renal or hepatic toxicity. The causality of adverse events with respect to bFGF is unknown; however, the unexplained hemodynamic and electrophysiologic events within 3 days of bFGF administration suggest that its biologic effects persist well beyond its clearance from the serum. We conclude: IC bFGF at doses of 3-30 mcg/kg is generally well tolerated in pts with coronary disease and stable angina. Higher doses were associated with unacceptable side effects. Further clinical studies are warranted to assess biologic activity.